Microfluidic manifold and methods of use thereof

Abstract

An extraction chamber includes a main channel, a plasma channel, and a plurality of side channels fluidly connecting the main channel to the plasma channel. Each of the plurality of side channels has an average diameter of at most 200 μm at a narrowest cross section, and the extraction chamber has a separation efficiency of at least 95%. A multilevel extraction chamber, includes a main channel, a secondary channel fluidly connected to the main channel, a plasma channel fluidly connected to the secondary channel, a first set of a plurality of side channels fluidly connecting the main channel to the secondary channel, and a second set of a plurality of side channels fluidly connecting the secondary channel to the plasma channel. Each of the first set of side channels has an average diameter that is greater than the average diameter of each of the second set of side channels, and the extraction chamber has a separation efficiency of at least 95%.

What is claimed is: 
     
       1. A multilevel extraction chamber, comprising:
 a main channel, 
 a secondary channel fluidly connected to the main channel, 
 a plasma channel fluidly connected to the secondary channel, 
 a first set of a plurality of side channels fluidly connecting the main channel to the secondary channel, and 
 a second set of a plurality of side channels fluidly connecting the secondary channel to the plasma channel, 
 wherein each of the first set of side channels has an average diameter that is greater than the average diameter of each of the second set of side channels, 
 the main channel has an average diameter of 0.2-5 mm at a narrowest cross section, and 
 the first set of the plurality of side channels, and each of the second set of the plurality of side channel, each have an average diameter of 5-100 μm at the narrowest cross section. 
 
     
     
       2. The multilevel extraction chamber of  claim 1 , wherein the first set of the plurality of side channels, and the second set of the plurality of side channel, each have an average diameter of 5-30 μm at the narrowest cross section. 
     
     
       3. The multilevel extraction chamber of  claim 1 , wherein the main channel has an average diameter of 0.3-1.0 mm at a narrowest cross section. 
     
     
       4. The multilevel extraction chamber of  claim 1 , having a separation efficiency for whole blood of at least 95%. 
     
     
       5. The multilevel extraction chamber of  claim 1 , wherein the plasma channel has an average diameter of 1-1000 μm. 
     
     
       6. The multilevel extraction chamber of  claim 1 , further comprising an obstruction in the main channel. 
     
     
       7. The multilevel extraction chamber of  claim 1 . further comprising a plurality of obstructions in the main channel. 
     
     
       8. The multilevel extraction chamber of  claim 1 , further comprising means for internal flow rectification. 
     
     
       9. A microfluidic manifold, comprising:
 the multilevel extraction chamber of  claim 1 , and 
 a dilution chamber, comprising:
 a dilution channel having a first end and a second end, 
 a plasma inlet on the first end of the dilution channel, 
 a dilutant inlet on the first end of the dilution channel, and 
 a diluted plasma outlet on the second end of the dilution channel, 
 
 wherein the plasma inlet and dilutant inlet are fluidly connected to the dilution channel, and the diluted plasma outlet is fluidly connected to the dilution channel, and 
 wherein the extraction chamber is fluidly connected to the dilution chamber. 
 
     
     
       10. The microfluidic manifold of  claim 9 , further comprising means for internal flow rectification in the dilution channel. 
     
     
       11. The microfluidic manifold of  claim 9 , wherein the microfluidic manifold comprises at least one polymer selected from the group consisting of polylactic acid (PLA), acrylonitrile butadiene styrene (ABS), nylon, polyethylene terephthalate glycol-modified (PETG), thermoplastic polyurethane (TPU) and polydimethylsiloxane (PDMS). 
     
     
       12. The microfluidic manifold of  claim 9 , wherein the microfluidic manifold comprises polydimethylsiloxane (PDMS). 
     
     
       13. The microfluidic manifold of  claim 9 , further comprising a mixture of heparin and glutaraldehyde coated on the extraction chamber, and/or the dilution chamber. 
     
     
       14. The microfluidic manifold of  claim 9 , wherein the manifold is capable of extracting plasma from less than 5 mL of whole blood. 
     
     
       15. A method of preparing a diluted plasma sample from a whole blood sample, comprising:
 pumping a whole blood sample into the microfluidic manifold of  claim 9 , 
 extracting a plasma sample from the whole blood sample, and 
 diluting the plasma sample. 
 
     
     
       16. The method of  claim 15 , wherein the sample of whole blood is diluted prior to extracting plasma from the sample of whole blood.